Towards a decade of detecting new analogues of sildenafil, tadalafil and vardenafil in food supplements: a history, analytical aspects and health risks

J Pharm Biomed Anal. 2012 Oct;69:196-208. doi: 10.1016/j.jpba.2012.02.014. Epub 2012 Mar 8.

Abstract

The scale at which erectile dysfunction (ED) medicines are obtained outside of the official health system rivals and possibly exceeds legitimate sales. According to literature a high-risk segment of this market is occupied by adulterated food supplements. The principle adulterants identified were structural analogues of the registered ED drugs sildenafil, tadalafil, and vardenafil. Currently, at least 46 different analogues have been reported and still more are expected. The intellectual origin of analogues was found in patent literature which described the drug discovery process. Patent literature offers a flexible approach to synthesize hundreds of analogues. Most of the analogues currently known had long been disclosed in patent literature. Screening for (new) analogues is best carried out by using advanced LC-MS/MS techniques that focus on marker fragment ions. Analogues are experimental drugs in essence because most have no known efficacy or safety profile. Their use in seemingly harmless food supplements is expected to cause serious adverse effects. However, few reports have emerged in literature on actual harm. Considering the exposure to analogues and their adverse effects being unknown a gross underreporting of complaints is expected.

Publication types

  • Review

MeSH terms

  • Carbolines / chemistry*
  • Chemistry Techniques, Analytical
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / chemistry
  • Dietary Supplements*
  • Drug Contamination*
  • Erectile Dysfunction / drug therapy
  • Humans
  • Imidazoles / chemistry*
  • Ions
  • Male
  • Models, Chemical
  • Phosphodiesterase 5 Inhibitors / therapeutic use
  • Piperazines / chemistry*
  • Purines / chemistry
  • Sildenafil Citrate
  • Sulfones / chemistry*
  • Tadalafil
  • Triazines / chemistry
  • Vardenafil Dihydrochloride
  • Vasodilator Agents / therapeutic use

Substances

  • Carbolines
  • Imidazoles
  • Ions
  • Phosphodiesterase 5 Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Triazines
  • Vasodilator Agents
  • Vardenafil Dihydrochloride
  • Tadalafil
  • Sildenafil Citrate
  • Cyclic Nucleotide Phosphodiesterases, Type 5